The proposed studies will focus on: (1) biochemical characterization of the cellular receptor for TRH. The associated guanine nucleotide binding protein, Gp, will also be investigated in pituitary cells and in Xenopus laevis oocytes; (2) regulation of [Ca]i by TRH. Emphasis will be on second messenger molecules, transfer of Ca between intracellular compartments, and on the functional relationship between oscillations in [Ca]i and hormone secretion; and (3) regulation of the rat TRH-R. After cloning the rat TRH-R cDNA, studies will focus on the hormonal regulation of the TRH-R in lactotropic cells, the developmental pattern of TRH-R expression in the central nervous system, and the functional role of TRH and its receptor in the fetal pancreas.